(R)-chiral halogenated substituted fused heterocyclic amino compounds useful for inhibiting cholesterol ester transfer protein activity

Abstract

The invention relates to substituted aryl and heteroaryl (R)-Chiral Halogenated 1-Substitutedamino-(n+1)-Alkanol compounds useful as inhibitors of cholesteryl ester transfer protein (CETP; plasma lipid transfer protein-I) and compounds, compositions and methods for treating atherosclerosis and other coronary artery diseases. Novel high yield, stereoselective processes for the preparation of the chiral substituted alkanol compounds from chiral and achiral intermediates are described.

1. A method of treating a CETP-mediated disorder in a subject by administering a therapeutically effective amount of the compound (2R)-3-[[3-(4-chloro-3-ethylphenoxy)phenyl][[3-(1,1,2,2- tetrafluoroethoxy)phenyl]-methyl]amino]- 1,1,1-trifluoro-2-propanol or a pharmaceutically acceptable salt thereof. 
     
     
       2. The method of  claim 1  further characterized by treating coronary artery disease in a subject by administering a therapeutically effective amount of the compound (2R)-3-[[3-(4-chloro-3-ethylphenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-methyl]amino]-1,1,1-trifluoro -2-propanol or a pharmaceutically acceptable salt thereof. 
     
     
       3. The method of  claim 1  further characterized by treating a cerebral vascular accident in a subject by administering a therapeutically effective amount of the compound (2R)-3 -[[3-(4-chloro-3-ethylphenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-methyl]amino]- 1,1,1-trifluoro-2-propanol or a pharmaceutically acceptable salt thereof. 
     
     
       4. The method of  claim 1  further characterized by treating dyslipidemia in a subject by administering a therapeutically effective amount of the compound (2R)-3-[[3-(4-chloro-3-ethylphenoxy)phenyl][[3-(1,1,2,2- tetrafluoroethoxy)phenyl]-methyl]amino]-1,1,1-trifiuoro-2-propanol or a pharmaceutically acceptable salt thereof.